Dasatinib is a cyclic protein tyrosine kinase inhibitor indicated for newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase; adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and, adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. It is also being evaluated for use in numerous other cancers, including advanced prostate cancer.
Dasatinib is chemically described as N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide. It is approved in USFDA as SPRYCEL™ and is chemically mentioned in the label as N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, monohydrate.

It is a white to off-white powder, insoluble in water and slightly soluble in alcoholic solvents like ethanol and methanol.
Das et al, in U.S. Pat. No. 6,596,746 B1 provided the first disclosure of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide or Dasatinib, which also describes the process for preparing Dasatinib.
Further to this Lajeunesse et al. in U.S. Pat. No. 7,491,725 B2 provided the crystalline monohydrate, crystalline butanol solvate, crystalline ethanol solvate and neat forms of Dasatinib. U.S. Pat. No. 7,491,725 B2 also provides processes for the preparation of these mentioned forms of Dasatinib. Scheme I shows one of the process for the preparation of Dasatinib according to U.S. Pat. No. 7,491,725 B2.

It has been mentioned in this patent that Dasatinib can be further converted into its monohydrate by methods such as heating the Dasatinib free base solution in aqueous ethanol solution; or by seeding aqueous acetate salt of Dasatinib or aqueous suspension of Dasatinib with its monohydrate form and heating; or treating a solution of Dasatinib in solvents such as NMP or DMA with water. However, the yield % of the mentioned processes is quite low (˜80%), to be economical for industrial set-up.
Further review of the available literature regarding Dasatinib monohydrate discloses various other processes for its preparation but due to one or more drawbacks with respect to the production of side products, the use of expensive coupling reagents, less than desirable yields, and the need for multiple reaction steps, most of them are not particularly convenient and economical for industrial scale-up.
Hence, there is an unmet need to develop improved, cost-effective and industrially amenable processes for the preparation of Dasatinib monohydrate involving less number of steps and providing higher yield of end product with better purity.
Therefore, inventors of the present application provide a simple high yielding process for preparation of highly pure Dasatinib monohydrate, which overcomes the disadvantages associated with prior disclosed literature methods.